Category Archives: Endocannabinoid System

A new face of endocannabinoids in pharmacotherapy. Part I & II

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“A new face of endocannabinoids in pharmacotherapy. Part I: Protective role of endocannabinoids in hypertension and myocardial infarction.

Cannabinoids are compounds which were first isolated from the Cannabis sativa plant. For thousands of years they have been used for treatment of numerous diseases.

Currently, synthetic cannabinoids and endocannabinoids are also known. Cannabinoid receptors, endocannabinoids and the enzymes that catalyze their synthesis and degradation constitute the endocannabinoid system which plays an important role in functioning of the cardiovascular system.

The results obtained to date suggest the involvement of endocannabinoids in the pathology of many cardiovascular diseases, including myocardial infarction, hypertension and hypotension associated with hemorrhagic, endotoxic, and cardiogenic shock. Cardioprotective effect and dilation of coronary vessels induced by endocannabinoids deserve special attention.

It cannot be excluded now that in the future our better understanding of cannabinoid system will allow to develop new strategies for treatment of cardiovascular diseases.”

http://www.jpp.krakow.pl/journal/archive/04_14/pdf/171_04_14_article.pdf

“A new face of endocannabinoids in pharmacotherapy. Part II. Role of endocannabinoids in inflammation-derived cardiovaascular diseases.

 Endocannabinoids play an important role in cardiovascular diseases caused by inflammatory disorders. Endocannabinoids are endogenous bioactive lipids that activate cannabinoid receptors and together with enzymes responsible for their synthesis and degradation constitute endocannabinoid system.

The results obtained to date suggest the involvement of endocannabinoids in the pathology of many cardiovascular diseases associated with inflammation, such as atherosclerosis, restenosis, chemotherapy-induced myocardial injury, diabetic and hepatic cirrhosis cardiomyopathy.

Our better understanding of cannabinoid system may result in the development of new strategies for the treatment of such disorders.”

http://www.jpp.krakow.pl/journal/archive/04_14/pdf/183_04_14_article.pdf

Getting High on the Endocannabinoid System

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“The endogenous cannabinoid system—named for the plant that led to its discovery—is one of the most important physiologic systems involved in establishing and maintaining human health.

Endocannabinoids and their receptors are found throughout the body: in the brain, organs, connective tissues, glands, and immune cells. With its complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind.

By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.

…either stimulating or inhibiting the endocannabinoid system could have beneficial effects.

The most direct route of THC administration is by smoking marijuana or other forms of cannabis. Yet purified, FDA-approved medicinal preparations of THC are available in pill form… Why not just take a pill? There are several reasons that some patients prefer puffing over swallowing. One quantitatively minor factor is potential lethality.

It is possible to get a fatal overdose by swallowing too many THC pills at once, whereas documented evidence of death simply from smoking too much cannabis does not seem to exist.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997295/

Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex-dependent social interest in mice.

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“Abnormalities in social behavior are found in almost all psychiatric disorders, such as anxiety, depression, autism, and schizophrenia. Thus, comprehension of the neurobiological basis of social interaction is important for a better understanding of numerous pathologies and improved treatments.

Several findings have suggested that an alteration of cannabinoid receptor type 1 (CB1) receptor function could be involved in the pathophysiology of such disorders…

In conclusion, we provide evidence that CB1 receptors specifically modulate the social investigation of female mice in a neuronal subtype-specific manner.”

http://www.ncbi.nlm.nih.gov/pubmed/24698342

Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver.

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“Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22.

Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects.

In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17.

These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production.”

http://www.ncbi.nlm.nih.gov/pubmed/23813495

Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction

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“Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions..

Cannabinoids are compounds derived from the Cannabis sativa plant and exert many effects on the immune system. Cannabinoids have potential as therapeutic agents in several different disease conditions, including experimental autoimmune hepatitis, Multiple Sclerosis, and Graft vs. Host Disease…

This report suggested a role of the endogenous cannabinoid system in regulation of allergic inflammation.

These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body employs to down-regulate immune response to foreign antigens as well as combat autoimmunity.

Targeting of this system could yield valuable therapeutics in the future.”

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093954

Pharmacology and toxicology of Cannabis derivatives and endocannabinoid agonists.

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“For centuries Cannabis sativa and cannabis extracts have been used in natural medicine.

Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis.

In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma.

Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications.

The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.”

http://www.ncbi.nlm.nih.gov/pubmed/19832688

Targeting the endocannabinoid system in the treatment of fragile X syndrome.

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“Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism, is caused by the silencing of the FMR1 gene, leading to the loss of fragile X mental retardation protein (FMRP), a synaptically expressed RNA-binding protein regulating translation.

The endocannabinoid system (ECS) is a key modulator of synaptic plasticity, cognitive performance, anxiety, nociception and seizure susceptibility, all of which are affected in FXS. The cannabinoid receptors CB1 (CB1R) and CB2 (CB2R) are activated by phospholipid-derived endocannabinoids, and CB1R-driven long-term regulation of synaptic strength, as a consequence of mGluR5 activation, is altered in several brain areas of Fmr1 knockout mice.

We found that CB1R blockade in male Fmr1 knockout (Fmr1(-/y)) mice through pharmacological and genetic approaches normalized cognitive impairment, nociceptive desensitization, susceptibility to audiogenic seizures, overactivated mTOR signaling and altered spine morphology, whereas pharmacological blockade of CB2R normalized anxiolytic-like behavior. Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5.

Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS.”

http://www.ncbi.nlm.nih.gov/pubmed/23542787

Role of the cannabinoid system in the transit of beta-amyloid across the blood-brain barrier.

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“Emerging evidence suggests beta-amyloid (Aβ) deposition in the Alzheimer’s disease (AD) brain is the result of impaired clearance, due in part to diminished Aβ transport across the blood-brain barrier (BBB). Recently, modulation of the cannabinoid system was shown to reduce Aβ brain levels and improve cognitive behavior in AD animal models.

The purpose of the current studies was to investigate the role of the cannabinoid system in the clearance of Aβ across the BBB..

The current studies demonstrate, for the first time, a role for the cannabinoid system in the transit of Aβ across the BBB. These findings provide insight into the mechanism by which cannabinoid treatment reduces Aβ burden in the AD brain and offer additional evidence on the utility of this pathway as a treatment for AD.”

http://www.ncbi.nlm.nih.gov/pubmed/23831388

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Effect of an acute consumption of a moderate amount of ethanol on plasma endocannabinoid levels in humans.

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“Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans…

AEA, 2-AG and plasma glucose levels were significantly reduced after red wine consumption.

Water intake had no significant effect on AEA  but resulted in a gradual reduction in 2-AG concentrations…

The consumption of a moderate amount of red wine reduces plasma AEA and 2-AG concentrations, whereas the volume and caloric equivalent of the sugar containing, non-alcoholic liquid grape juice does not affect plasma ECs. Plain water has a differential effect on the ECS by reducing 2-AG concentrations without affecting AEA.”

http://www.ncbi.nlm.nih.gov/pubmed/22278319

Exercise, Manual Therapy, and the Endocannabinoid System: Why we’re all inherently potheads

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“Have you ever heard of the digestive system? The lymphatic system? How about the muscular and nervous systems? Of course you have. Science has been studying them for years, making breakthroughs in our understanding of their inner workings that have lead to advancements benefited humanity in ways we now take for granted.

How about the endocannabinoid system? Have you heard of that?  If your profession has nothing to do with the biological sciences, I would expect the answer to be no (save a few individuals).  Don’t feel bad however, I have asked this question to many health and medical professionals that I have taught over the years and have received many a blank stare or look of confusion.

What if I were to tell you that this biological system permeates the entire human body with receptors located in skeletal muscle, the digestive tract, adipose (fat) tissue, and throughout the peripheral and central nervous systems (including the brain)? Again, you would question why this system is not studied, discussed, or even mentioned in most in physiology/health classes.

What if I were to tell you that the Endocannabinoid system (or ECS):

–   Helps regulate the central control of energy balance

–   Helps regulate metabolic processes (including storage)

–   Plays a key role in the maintenance of bone mass

–   Regulates intestinal motility

–   Promotes/regulates sleep

–   Is involved in neuromodulation and immunomodulation in the immune system

–   Is involved in modulating insulin sensitivity

–   Is involved in the regulation of pain signaling

–   And much more”

http://functionalanatomyblog.com/2014/03/27/exercise-manual-therapy-and-the-endocannabinoid-system-why-were-all-inherently-potheads/

“Exercise activates the endocannabinoid system.”  http://www.ncbi.nlm.nih.gov/pubmed/14625449

“Exercise-induced endocannabinoid signaling is modulated by intensity.”  http://www.ncbi.nlm.nih.gov/pubmed/22990628

“Effects of exercise stress on the endocannabinoid system in humans under field conditions.”   http://www.ncbi.nlm.nih.gov/pubmed/22101870